FDA Issues Statement on Long-Term Clopidogrel Tx and Risk of Death

FDA Issues Statement on Long-Term Clopidogrel Tx and Risk of Death

Based on reviews of the Dual Antiplatelet Therapy (DAPT) trial and several other large, long-term clinical trials, the FDA has concluded that there is no evidence of either a harmful or beneficial effect of clopidogrel on all-cause mortality or cancer-related deaths in a population with, or at risk for, coronary artery disease.

In order to investigate the signals of increased risk of death and cancer-related death from the DAPT trial, the FDA evaluated the DAPT trial and performed trial-level meta-analyses of other large, long-term trials that had available data on rates of death, rates of death from cancer, or rates of cancer adverse events. Trials included in the meta-analyses had a clopidogrel plus aspirin arm (long term was 12 months or longer), a comparator arm of either aspirin alone or short-term clopidogrel plus aspirin (6 months or less), and had a planned follow-up of at least one year. The FDA focused its investigation on clopidogrel because findings from the DAPT trial suggested an increase in the risk of death and cancer death in that group.

Study results showed that long-term (≥12 months) dual antiplatelet therapy with clopidogrel + aspirin do not appear to influence the overall risk of death vs. short-term (≤6 months) clopidogrel + aspirin or aspirin alone. No increase in the risks of cancer-related deaths or cancer-related adverse events with long-term treatment were observed.

The FDA is working with drug manufacturers to reflect the results of the mortality meta-analysis in an updated label. The FDA recommends that patients do not discontinue use of clopidogrel or other antiplatelets because it may result in an increased risk of heart attack or blood clots.

When selecting antiplatelet therapy for patients with an acute coronary syndrome who are managed with coronary stent implantation, prescribers should consider that prasugrel and ticagrelor have been shown to be superior to clopidogrel when used in this patient population. In addition, in patients with a history of myocardial infarction one to three years prior to study enrollment, ticagrelor has also been shown to reduce the risk of cardiovascular death, myocardial infarction, and stroke.